This study is aimed at elucidating the composition of the proteinpolysaccharide complex present in the matrix of cartilage and clarifying changes that occur in this complex during development, with aging, and in disease (i.e. osteoarthritis). New gentle techniques will be used to isolate proteinpolysaccharide complex from cartilage during the various stages of development, aging and disease. The components of the complex will be carefully isolated, purified, and characterized. Changes will be looked for both in the proteinpolysaccharide and "glycoprotein" fractions of the complex. Immunological methods will be used throughout these studies to facilitate the identification, isolation and characterizaton of these fractions. It should be possible to determine whether the changes reported to occur in polysaccharide composition during development, with aging and in disease are due to change in the core protein of the proteinpolysaccharide or merely reflect a change in type of polysaccharide chain attached to the same protein core. Since the "glycoprotein" fraction is probably involved in the aggregation of cartilage proteinpolysaccharide, changes in this fraction may produce significant alterations in the properties of the cartilage matrix during development, with aging and in disease. Purified antigens prepared from both the proteinpolysaccharide and "glycoprotein" fractions of cartilage proteinpolysaccharide complex will be used to look for both humoral and cell-mediated hypersensitivity in relapsing polychondritis, rheumatoid arthritis, systemic lupus and other connective tissue diseases. The objective will be to ascertain whether any of the immune phenomena in connective tissue diseases are directed toward these purified connective tissue components.